1. Field of the Invention
The present invention relates to coating active pharmaceutical ingredients for controlled release or applications associated with controlled release such as taste masking. In particular, it is directed to a particulate pharmaceutical formulation coated with both a water soluble or swellable coating material and a substantially water insoluble polymer and a process of producing the same.
2. Description of the Related Technology
Compliance with medication requirements is a significant challenge for patients who have difficulties swallowing, such as young children, the very elderly and patients with dysphagia. The pharmaceutical industry has developed a number of drug delivery protocols to address this challenge, including rapid in-mouth disintegrating tablets, tablets which disintegrate in liquid prior to ingestion, liquids and syrups, gums and even transdermal patches. Unfortunately, each of these methods has its own problems. For example, transdermal patches can be inconvenient or uncomfortable and can be quite expensive to produce. The flux of drug through the skin can also create complex dosing issues.
Masking the undesirable taste of an active pharmaceutical ingredient (API) will make it pleasant to chew and swallow, therefore easier for patients to comply with their medication requirements. Microencapsulation is a taste masking process in which a particle is encased by coating, and therefore may be capable of masking the taste of API. Microencapsulation has been used for many commercial applications such as in pharmaceuticals, cosmetics, agricultural products, and copier toners.
Many microencapsulation methods require solvents, such as wet methods and spray drying methods. The solvents, especially organic solvents, may result in environmental pollution and hazardous conditions during the manufacturing process. Organic solvents also add extra cost in addition to increasing energy costs and requiring relatively long processing times. Thus, it is desirable to develop taste masking methods that do not use solvents.
Two types of methods have been developed for this purpose, methods using plasticizers and methods using mechanical energy to apply the coating. The methods employing plasticizers are limited to coarse particles/granules/pellets/tablets with a size greater than 500 microns. Mechanical coating methods may break the core particles into undesirably small particles and are typically limited to the application to coating of robust particles with relatively thin coating layers of only about 1-5 microns in thickness. The advantages of mechanical coating are that typically no plasticizer and no thermal treatment are required to prepare the coating.
Obara et al. discloses a dry coating method using polymer powders (Obara, S; Maruyama, N; Nishiyama, Y; Kokubo, H., “Dry coating: an innovative enteric coating method using a cellulose derivative,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 47, 1999, pages 51-59). This method involves direct feeding of polymer powder and simultaneous spraying of plasticizing agent, with neither an organic solvent nor water, using a centrifugal granulator, fluidized bed, or tablet-coating machine. The method requires a higher loading of coating to achieve gastric resistance compared with a conventional coating, but the processing time was dramatically reduced.
Kim et al. discloses a mechanical dry coating process (Kim, J; Satoh, M; Iwasaki, T., “Mechanical-dry coating of wax onto copper powder by ball milling,” Materials Science and Engineering A, Vol. 342, 2003, pages 258-263). The process produces an oxidation resistant film of polymer wax on spherical copper particles (median diameter of 69.1 μm) using a conventional ball milling process. The polymer wax functions as a sealant material for filling the cavities of the hard wax, which can effectively stabilize the coating and enhance the degree of coverage.
Wang et al. discloses a coating process wherein ascorbic acid particulates are milled and coated simultaneously with fine wax particles using fluid energy milling (Wang, P; Zhu, Linjie; Teng, S; Zhang, Q; Young, M W; Gogos, C., “A novel process for simultaneous milling and coating of particulates,” Powder Technology, Vol. 193, 2009, 65-68). During the milling process, ascorbic acid particulates collide with each other, wax powder particles and the wall to produce fine particles within a discrete polymer coating. This novel process has several advantages such as elimination of solvent usage, reduction of agglomeration, and vastly improved production efficiency. The core particles are also typically ground to fine particles of about 10 microns in diameter.
Zhang et al. discloses a fluid energy-based method and apparatus for simultaneously milling and coating coarse particles (Zhang, Q; Wang, P; Qian, Z; Zhu, Linjie; Gogos, C., “Simultaneous Milling and Coating of Inorganic Particulates with Polymeric Coating Materials Using a Fluid Energy Mill,” Polymer Engineering and Science, Vol. 50, 2010, pages 2366-2374). The coating materials include three micron-sized particles—carnauba wax, polyethylene (PE), and polytetrafluoroethylene (PTFE) particles, and one type of nanoparticle. The polymeric coating, which functions as a lubricant and cushioning layer, absorbs part of the kinetic energy and produces coated particles with larger particle sizes. Again the core particles are typically ground to fine powders in this process.
U.S. Pat. No. 7,862,848 discloses a method and apparatus for dry coating solid dosage forms. The method includes the steps of placing solid dosage forms in a rotatable, electrically grounded housing, and spraying a film-forming polymer powder composition into the housing during rotation thereof to form a polymer coating on the solid dosage forms. The polymer powder composition is sprayed using an electrostatic spray gun. Curing of the polymer coating on the solid dosage form is also required.
U.S. Pat. No. 5,628,945 discloses a method of dry coating core particles with a controlled distribution of substances in a solid state. Ball milling and mechanofusion are used to produce granulated ceramic particles in a metal-organic matrix. Heat treatment and multiple processing steps are required to achieve granules of microencapsulated particles. The method produces a structured coating and a controlled level of subdivision on the core particles. The method can also be used to agglomerate the microcapsules into granules.
There remains a need for improved solventless processes for coating API's. More specifically, solventless processes for coating API's having acceptable processing times are desirable. In addition, a process capable of coating fine particles to provide a product with improved mouth feel and without attrition/breakage is also desirable. Such coatings should also provide release of the API in a relatively short time once the API is ingested or a more gradual release of the API for extended release formulation.